[3H]BHDP as a novel and selective ligand for σ1 receptors in liver mitochondria and brain synaptosomes of the rat

The binding profile of [³H]BHDP ([³H]N-benzyl-N′-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine) was evaluated. [³H]BHDP labelled a single class of binding sites with high affinity (K_d=2–3 nM) in rat liver mitochondria and synaptic membranes. The pharmacological characterization of these sites using σ reference compounds revealed that these sites are σ receptors and, more particularly, σ1 receptors. Indeed, BHDP inhibited [³H]pentazocine binding, a marker for σ1 receptors, with high affinity in a competitive manner. BHDP is selective for σ1 receptors since it did not show any relevant affinity for most of the other receptors, ion channels or transporters tested. Moreover, in an in vitro model of cellular hypoxia, BHDP prevented the fall in adenosine triphosphate (ATP) levels caused by 24 h hypoxia in cultured astrocytes. Taken together, these results demonstrate that [³H]BHDP is a potent and selective ligand for σ1 receptors showing cytoprotective effects in astrocytes. [Copyright &y& Elsevier]